It is proposed to continue to investigate whether the application of circadian time-based chemotherapy can minimize drug toxicity and maximize its anticancer activity. This work will focus entirely upon the study of the circadian timing of infusional fluoropyrimidine chemotherapy. A multi-center clinical study utilizing single agent fluorodeoxyuridine will be performed in patients with metastatic progressive measurable renal cell carcinoma (RCC). This application expands the clinical study of chronopharinacodynamic questions from Albany Medical College to five additional centers with great independent interest in fluoropyrimidine chronopharmacology and/or kidney cancer. Dr. Robert Diasio at the University of Alabama in Birmingham, Dr. Robert Huben at Roswell Park Memorial Institute, Dr. Ace Allen at the University of Kansas, Dr. Georg Bjarnason at the Toronto-Bayview Hospital and Dr. Elwin Fraley at the University of Minnesota have each pledged to participate in the proposed study. Good performance status, previously untreated patients with measurable, progressive, metastatic RCC will be studied using a two-armed design which randomly assigns circadian infusion pattern. Based upon extensive preclinical murine and clinical phase I and phase II study of infusional FUDR in nearly 250 patients this agent will be delivered either by standard 14-day constant rate infusion or multi-step quasi-sinusoidal infusion peaking between 8 p.m. and 2 a.m. each day, repeated every 28 days. Because of well documented inter-individual differences in fluoropyrimidine tolerance and because of the likely importance of fluoropyrimidine dose intensity each study will employ individual FUDR dose escalation, allowing each evaluable patient to receive her or his highest safely tolerated fluoropyrimidine dose intensity. This clinical study will test the effect of circadian infusion shape upon: drug toxicity; maximum tolerated dose; mean dose intensity; frequency, quality and duration of tumor response; and patient survival.